PAIR2
PAIR2 is a highly selective inhibitor targeting the kinase domain of human IRE1α, with a Ki value of 8.8 nM against human IRE1α. PAIR2 fully occupies the ATP-binding site of the IRE1α kinase domain, partially antagonizes the ribonuclease activity of IRE1α, specifically inhibits regulated IRE1α-dependent decay (RIDD) and its mediated substrate cleavage, while preserving the splicing function of Xbp1 mRNA. PAIR2 also promotes the differentiation of B cells into plasma cells, blocks IRE1α-induced cell apoptosis, and restores the expression of Fgfr2 mRNA in AT2 cells. PAIR2 effectively reaches a steady-state concentration in the lung tissues of Mus musculus, and serves as an important tool for investigating the function of the IRE1α signaling pathway in diseases such as pulmonary fibrosis.
For research use only. We do not sell to patients.
- CAS No.: 2771006-54-1
- Formula: C27H26F4N6O3S
- Molecular Weight:590.59
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
-
Biological Activity
-
Chemical Information
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
|
IRE1α 8.8 nM (Ki) |
FGFR2 |
PAIR2 (1-10 μM; 1 h + 6 h doxycycline (HY-N0565)) dose-dependently blocks doxycycline-induced autophosphorylation of IRE1α in INS-1::PCMV/2xTetO cells[1].
PAIR2 (0.5-10 μM; 1 h+2 h DTT (HY-15917)) maintains XBP1 mRNA splicing in parental INS-1 cells subjected to DTT stress[1].
PAIR2 (2 μM; 24 h Thapsigargin (HY-13433)) rescues Fgfr2 mRNA expression in serum-free, feeder-free primary mouse AT2 organoids under Thapsigargin stress, while preserving IRE1α-mediated Xbp1 splicing[2].
PAIR2 (2 μM; 3-d) fails to prevent the conversion of primary serum-free, feeder-free mouse AT2 cells to DATCs when pemigatinib directly blocks the Fgfr signaling pathway[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Cell Line:INS-1::PCMV/2xTetO rat insulinoma cells (doxycycline-inducible IRE1α overexpression)
-
Concentration:1, 3, 10 μM
-
Incubation Time:1 h (PAIR2 pre-incubation); 6 h (doxycycline treatment)
-
Result:Dose-dependently blocked doxycycline-induced IRE1α autophosphorylation, reducing phosphorylated IRE1α levels to near baseline at concentrations ≥3 μM, with equivalent potency to KIRA8.
-
Cell Line:parent INS-1 rat insulinoma cells
-
Concentration:0.5, 1, 3, 10 μM
-
Incubation Time:1 h (PAIR2 pre-incubation); 2 h (DTT treatment)
-
Result:Preserved DTT-induced XBP1 mRNA splicing at all tested concentrations, with no significant reduction in splicing percentage relative to DTT-only treated cells (all P values > 0.05, non-significant).
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:C57BL/6 (10-20 week-old, both male and female, bleomycin-induced pulmonary fibrosis)[2]
-
Dosage:30 mg/kg
-
Administration:i.p.; twice daily; starting 1 day before bleomycin exposure and continuing through study end
-
Result:Reduced fraction of trace+Krt8+ / trace+ cells compared to vehicle control at day 10 post-bleomycin exposure.
Significantly lowered lung hydroxyproline content and reduced fibrillar collagen deposition via picrosirius red staining at day 14 post-bleomycin exposure.
Derepressed expression of canonical RIDD target Bloc1s1 in lung tissue.
Did not significantly affect Xbp1 splicing.
Chemical Information
-
CAS No. 2771006-54-1
-
Molecular Weight 590.59
-
Formula C27H26F4N6O3S
-
SMILES
CC(C(F)=C(NS(CC(F)(F)F)(=O)=O)C1=C2C=CC=C1)=C2OC3=NC=CC=C3C4=NC(N[C@H]5CCCNC5)=NC=C4
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Feldman HC, et al. ATP-competitive partial antagonists of the IRE1α RNase segregate outputs of the UPR. Nat Chem Biol. 2021;17(11):1148-1156. [Content Brief]
[2]. Auyeung VC, et al. Pharmacologic inhibition of IRE1α-dependent decay protects alveolar epithelial identity and prevents pulmonary fibrosis in mice. J Clin Invest. 2025;135(20):e184522. Published 2025 Oct 15. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Powered by Bioz